Blood consists of special unbound cells dispersed in a plasma medium. The contents of the cell are separated from the surrounding plasma by so-called plasma membranes. These membranes are made up of phospholipids in the form of a double layer and associated proteins which partially penetrate this double layer or protrude from it.
The various phospholipids are not randomly distributed over the outer and inner shell of the double layer but are held by the cell in an asymmetric configuration (Op den Kamp, J. A., F. Ann. Rev. Biochem. 48:47-71 (1979); Zwaal, R. F. A., Biochim. Biophs. Acta 515:163-205 (1978)). Whereas phosphatidyl choline (PC) and sphigomyelin (SPH) are the dominating species of the outer shell, phosphatidyl serine (PS), phosphatidyl ethanolamine (PE) and phosphatidyl inositol (PI) are located predominantly in the inner coat, facing the cytosol. This energy-consuming state of asymmetry is of exceptional physiological importance. PC and SPH are the most inert species of the phospholipid family and in stark contrast to the other species show exceptionally neutral behavior in the presence of the plasma components. This reactive inertia of the outer coat relative to the plasma proteins is the absolute prerequisite for ensuring that the blood remains liquid. Special plasma proteins which belong to the coagulation cascade, namely the so-called coagulation factors, are in fact able to convert liquid blood into a solid state when they are activated (Jackson & Nemerson, Ann. Rev. Biochem. 49:765-811 (1980)). These coagulation factors can be activated by phospholipids such as phosphatidyl serine.
In many cases, e.g. after injury to a blood vessel, it is necessary, not to mention crucial to survival, for the coagulation factors to be activated. In such a situation, a special blood cell, called the platelet, can give up its membrane asymmetry by activation mechanisms which transport phosphatidyl serine to the outer coat, where it aids the activation of the coagulation factors (Bevers, E. M., et al., Biochim. Acta 736:57-66 (1983)).
This systematic change in the phospholipid composition of the outer coat of the platelet plasma membrane is of major physiological importance in hemostasis, as indicated for example by the Scott syndrome (Rosing, J., et al., Blood 65:1557-1561 (1985)).
However, physiology also includes pathology; thus, the homoeostasis of the blood may in some cases slip into a pathological state, as occurs in arterial, coronary and venous thrombosis.
These hemostatic disorders are usually idiopathic and make it impossible for doctors to predict their occurrence and develop preventive treatment.